ABSTRACT
BACKGROUND: Proactively monitoring infliximab levels is an emerging area of interest in pediatric Crohn's disease. There are only limited data on therapeutic drug monitoring for children with Crohn's disease. The goal of our study was to determine the utility of therapeutic drug monitoring in achieving clinical remission in a cohort of pediatric Crohn's disease patients receiving infliximab. METHODS: This prospective single-center study enrolled 37 patients with Crohn's disease at the start of infliximab infusions and monitored trough levels at 6-month intervals for 18 months. Each participant was matched to a historic control for the modified pediatric Crohn's disease activity index (mPCDAI) at baseline, age and sex. The primary outcome was an mPCDAI score of ≤7.5 at 6, 12 and 18 months. A multivariate logistic regression analysis was performed. RESULTS: Data were available for all 37 cases at 6 and 12 months and for 34 cases at 18 months. Demographics and disease characteristics were similar between groups. All 34 cases demonstrated clinical remission at 18 months (100% vs. 88%, P=0.114). Univariate and multivariate analyses did not show statistical significance. Dose intensification was seen more often in the cases at 18 months. CONCLUSION: All of our moderate-to-severe pediatric Crohn's disease patients who received prospective therapeutic drug monitoring of infliximab were in clinical remission at follow up, but this was not statistically significantly different from the 88% clinical remission rate of the control group.
ABSTRACT
PURPOSE OF REVIEW: Controlling T cell activity through metabolic manipulation has become a prominent feature in immunology and practitioners of both adoptive cellular therapy (ACT) and haematopoietic stem cell transplantation (HSCT) have utilized metabolic interventions to control T cell function. This review will survey recent metabolic research efforts in HSCT and ACT to paint a broad picture of immunometabolism and highlight advances in each area. RECENT FINDINGS: In HSCT, recent publications have focused on modifying reactive oxygen species, sirtuin signalling or the NAD salvage pathway within alloreactive T cells and regulatory T cells. In ACT, metabolic interventions that bolster memory T cell development, increase mitochondrial density and function, or block regulatory signals in the tumour microenvironment (TME) have recently been published. SUMMARY: Metabolic interventions control immune responses. In ACT, efforts seek to improve the in-vivo metabolic fitness of T cells, while in HSCT energies have focused on blocking alloreactive T cell expansion or promoting regulatory T cells. Methods to identify new, metabolically targetable pathways, as well as the ability of metabolic biomarkers to predict disease onset and therapeutic response, will continue to advance the field towards clinically applicable interventions.
